PEGylated liposomes: immunological responses

A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers u...

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Bibliographic Details
Published in:Science and technology of advanced materials 2019-12, Vol.20 (1), p.710-724
Main Authors: Mohamed, Marwa, Abu Lila, Amr S., Shimizu, Taro, Alaaeldin, Eman, Hussein, Amal, Sarhan, Hatem A., Szebeni, Janos, Ishida, Tatsuhiro
Format: Article
Language:English
Subjects:
101 Self-assembly / Self-organized materials, drug delivery system
30 Bio-inspired and biomedical materials
Accelerated blood clearance (ABC) phenomenon
Activation
anti-PEG IgM
Antibodies
Chemical compounds
complement activation
complement activation-related pseudoallergy (CARPA)
Focus on Nanotoxicology
hypersensitivity reactions (HSRs)
Immune system
Immunology
Lipids
Liposomes
PEGylated liposomes
Pharmacology
Polyethylene glycol
polyethylene glycol (PEG)
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Summary:A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.
ISSN:1468-6996
1878-5514
DOI:10.1080/14686996.2019.1627174